Clinical Research Papers:

Changes of circulating Th22 cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection

Dawei Cui, Fengyun Zhong, Jie Lin, Yidong Wu, Quan Long, Xianzhi Yang, Qiaoyun Zhu, Li Huang, Qifen Mao, Zhaoxia Huo, Zhe Zhou, Guoliang Xie, Shufa Zheng, Fei Yu and Yu Chen _

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Oncotarget. 2017; 8:29370-29382. https://doi.org/10.18632/oncotarget.14083

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Dawei Cui1,2,*, Fengyun Zhong3,*, Jie Lin4,*, Yidong Wu5, Quan Long1,2, Xianzhi Yang1,2, Qiaoyun Zhu1,2, Li Huang1,2, Qifen Mao1,2, Zhaoxia Huo1,2, Zhe Zhou1,2, Guoliang Xie1,2, Shufa Zheng1,2, Fei Yu1,2 and Yu Chen1,2

1 Department of Laboratory Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

2 Key Laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, China

3 Department of General Surgery, the Second Affiliated Hospital of Soochow University, Suzhou, China

4 Department of Clinical Laboratory, Center of Community Health Service of Qingbo Street, Hangzhou, China

5 Clinical Laboratory, Hangzhou Children’s Hospital, Hangzhou, China

* These authors have contributed equally to this work

Correspondence to:

Yu Chen, email:

Keywords: HFMD, EV71, circulating Th22 cell, circulating Th17 cell

Received: June 06, 2016 Accepted: December 16, 2016 Published: December 21, 2016


Interleukin (IL)-22+CD4+T (Th22) cells play crucial roles in the pathogenesis of autoimmune diseases and infectious diseases, although the role of Th22 cells remains largely unclear in children with hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71). This study aims to explore the role of circulating IL-22+IL-17A-CD4+T (cTh22) cells in children with EV71-associated HFMD. We found that during the acute stage of illness, the frequencies of cTh22 and circulating IL-22+IL-17A+CD4+T (IL-22+cTh17) cells in CD4+T cells infrom affected patients, and especially in severely affected patients, were significantly higher than in healthy controls (HC). The major source of IL-22 production was cTh22 cells, partially from cTh17 cells. Moreover, the protein and mRNA levels of IL-22, IL-17A, IL-23, IL-6, and TNF-α were significantly different among the mild patients, severe patients and HC, as well as AHR and RORγt mRNA levels. A positive correlation was found between plasma IL-22 levels and cTh22 cell frequencies, and cTh17 cell and IL-22+ cTh17 cell frequencies. Furthermore, the frequencies of cTh22 were significantly decreased in the convalescent patients. Our findings indicated that cTh22 cells could play critical roles in the pathogenesis of EV71 infection, and are potential therapeutic targets for patients with EV71-associated HFMD.

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